PseudoSegRT: efficient pseudo-labelling for intraoperative OCT segmentation

PURPOSE: Robotic ophthalmic microsurgery has significant potential to help improve the success of challenging procedures and overcome the physical limitations of the surgeon. Intraoperative optical coherence tomography (iOCT) has been reported for the visualisation of ophthalmic surgical manoeuvres, where deep learning methods can be used for real-time tissue segmentation and surgical tool tracking. However, many of these methods rely heavily on labelled datasets, where producing annotated segmentation datasets is a time-consuming and tedious task. METHODS: To address this challenge, we propose a robust and efficient semi-supervised method for boundary segmentation in retinal OCT to guide a robotic surgical system. The proposed method uses U-Net as the base model and implements a pseudo-labelling strategy which combines the labelled data with unlabelled OCT scans during training. After training, the model is optimised and accelerated with the use of TensorRT. RESULTS: Compared with fully supervised learning, the pseudo-labelling method can improve the generalisability of the model and show better performance for unseen data from a different distribution using only 2% of labelled training samples. The accelerated GPU inference takes less than 1 millisecond per frame with FP16 precision. CONCLUSION: Our approach demonstrates the potential of using pseudo-labelling strategies in real-time OCT segmentation tasks to guide robotic systems. Furthermore, the accelerated GPU inference of our network is highly promising for segmenting OCT images and guiding the position of a surgical tool (e.g. needle) for sub-retinal injections

Proliferative vitreoretinopathy (PVR) - The use of adjuvant therapy in the preventative treatment of PVR and the study of clinical and biological risk factors

Proliferative vitreoretinopathy (PVR) is a major cause of failure of retinal detachment surgery and is thought to complicate 5 to 10% of all detachments. This thesis has investigated the use of adjuvant therapy in the preventative treatment of PVR and the identification of clinical and biological risk factors involved in PVR. A prospective randomised control study was conducted comparing intravitreal infusion of either 5 Fluorouracil (5-FU) and heparin or placebo in high-risk patients undergoing primary vitrectomy for rhegmatogenous retinal detachment surgery. There were 87 patients in each group. The incidence of postoperative PVR was significantly lower (P=0.019) in the treatment group. Of the placebo group 26.4% (23/87) and 12.6% (11 /87) of the 5-FU/heparin group developed postoperative PVR. In the 5-FU/heparin group the number of patients undergoing more than one operation was 19.5% (17/87) and the number of reoperations due to PVR was 52.9% (9/17). In the placebo group the number of patients undergoing more than one operafion was 25.3% (22/87) and the number of reoperations due to PVR was 72.7% (16/22). Patients in the placebo treated group had a significantly worse visual acuity outcome (p=<0.05). This study also investigated the accuracy of a "predictive risk formula" for the development of PVR and to assess its use in a clinical setting. Complete data were available on 214 out of 220 patients. Nine point two percent of the low risk (12/130) and 27.4% (23/84) of the high risk patients developed postoperative PVR (p<0.0001). Further risk factor analysis was also performed on these patients. Multiple regression analysis revealed only the existence of preoperative PVR, higher levels of bFGF and protein to be significant independent risk factors (p<0.05) for the development of PVR. Combined multiple logistic regression on clinical and biological risk factors revealed only preoperative PVR to be a significantly independent risk factor (p=0.01) for the development of postoperative PVR

Immunopathology of intraocular silicone oil: retina and epiretinal membranes

AIMS: To determine the inflammatory response in retina and epiretinal membranes after intraocular silicone oil tamponade. METHODS: 14 proliferative vitreoretinopathy (PVR) epiretinal membranes, 33 retro‐oil epiretinal membranes, 19 retinectomies, 14 retro‐oil retinectomies and 37 idiopathic epiretinal membranes (controls) underwent immunohistochemical analysis using the avidin–biotin complex technique and a panel of monoclonal and polyclonal antibodies. The number of positive cells counted in five 0.5 mm diameter fields of immunohistochemical sections was graded on a score of 1–4. RESULTS: Macrophage cell counts were significantly greater in membranes with a history of exposure to silicone oil (p<0.001). An inflammatory response could be observed within 1 month of silicone oil exchange, and the intensity seemed to be unrelated to the duration of exposure. Macrophages were confined to epiretinal membranes on the surface of retinectomy specimens in 10 of 14 cases and intraretinal macrophages were observed only in specimens with gliotic retina. T and B lymphocytes were rarely seen in the specimens examined. Marked glial cell up regulation was observed in 11 of 16 retinectomy specimens and in 8 of 11 retro‐oil retinectomies. Glial cell content was variable in the membranes, but there was a trend of increased presence after exposure to silicone oil. CONCLUSION: This study has shown that the use of silicone oil is accompanied by an inflammatory reaction, primarily mediated by bloodborne macrophages. This response can be observed within 1 month of silicone oil injection and continues after silicone oil removal. Retinal surgeons should be aware of the potential secondary effects of intraocular silicone oil when they are considering its use (and removal) in vitreoretinal surgery

Efficacy, durability, and safety of intravitreal faricimab with extended dosing up to every 16 weeks in patients with diabetic macular oedema (YOSEMITE and RHINE): two randomised, double-masked, phase 3 trials

Background: To reduce treatment burden and optimise patient outcomes in diabetic macular oedema, we present 1-year results from two phase 3 trials of faricimab, a novel angiopoietin-2 and vascular endothelial growth factor-A bispecific antibody. Methods: YOSEMITE and RHINE were randomised, double-masked, non-inferiority trials across 353 sites worldwide. Adults with vision loss due to centre-involving diabetic macular oedema were randomly assigned (1:1:1) to intravitreal faricimab 6·0 mg every 8 weeks, faricimab 6·0 mg per personalised treatment interval (PTI), or aflibercept 2·0 mg every 8 weeks up to week 100. PTI dosing intervals were extended, maintained, or reduced (every 4 weeks up to every 16 weeks) based on disease activity at active dosing visits. The primary endpoint was mean change in best-corrected visual acuity at 1 year, averaged over weeks 48, 52, and 56. Efficacy analyses included the intention-to-treat population (non-inferiority margin 4 Early Treatment Diabetic Retinopathy Study [ETDRS] letters); safety analyses included patients with at least one dose of study treatment. These trials are registered with ClinicalTrials.gov (YOSEMITE NCT03622580 and RHINE NCT03622593). Findings: 3247 patients were screened for eligibility in YOSEMITE (n=1532) and RHINE (n=1715). After exclusions, 940 patients were enrolled into YOSEMITE between Sept 5, 2018, and Sept 19, 2019, and 951 patients were enrolled into RHINE between Oct 9, 2018, and Sept 20, 2019. These 1891 patients were randomly assigned to faricimab every 8 weeks (YOSEMITE n=315, RHINE n=317), faricimab PTI (n=313, n=319), or aflibercept every 8 weeks (n=312, n=315). Non-inferiority for the primary endpoint was achieved with faricimab every 8 weeks (adjusted mean vs aflibercept every 8 weeks in YOSEMITE 10·7 ETDRS letters [97·52% CI 9·4 to 12·0] vs 10·9 ETDRS letters [9·6 to 12·2], difference −0·2 ETDRS letters [−2·0 to 1·6]; RHINE 11·8 ETDRS letters [10·6 to 13·0] vs 10·3 ETDRS letters [9·1 to 11·4] letters, difference 1·5 ETDRS letters [−0·1 to 3·2]) and faricimab PTI (YOSEMITE 11·6 ETDRS letters [10·3 to 12·9], difference 0·7 ETDRS letters [−1·1 to 2·5]; RHINE 10·8 ETDRS letters [9·6 to 11·9], difference 0·5 ETDRS letters [−1·1 to 2·1]). Incidence of ocular adverse events was comparable between faricimab every 8 weeks (YOSEMITE n=98 [31%], RHINE n=137 [43%]), faricimab PTI (n=106 [34%], n=119 [37%]), and aflibercept every 8 weeks (n=102 [33%], n=113 [36%]). Interpretation: Robust vision gains and anatomical improvements with faricimab were achieved with adjustable dosing up to every 16 weeks, demonstrating the potential for faricimab to extend the durability of treatment for patients with diabetic macular oedema. Funding: F Hoffmann-La Roche.</p

Clinical Effectiveness of Intravitreal Therapy With Ranibizumab vs Aflibercept vs Bevacizumab for Macular Edema Secondary to Central Retinal Vein Occlusion A Randomized Clinical Trial

Importance:  The comparative clinical effectiveness of ranibizumab, aflibercept, and bevacizumab for the management of macular edema due to central retinal vein occlusion (CRVO) is unclear.Objective:  To determine whether intravitreal aflibercept or bevacizumab compared with ranibizumab results in a noninferior mean change in vision at 100 weeks for eyes with CRVO-related macular edema.Design, Setting, and Participants: This prospective, 3-arm, double-masked, randomized noninferiority trial (Lucentis, Eylea, Avastin in Vein Occlusion [LEAVO] Study) took place from December 12, 2014, through December 16, 2016, at 44 UK National Health Service ophthalmology departments. Inclusion criteria included age 18 years or older, visual impairment due to CRVO-related macular edema of less than 12 months with best-corrected visual acuity (BCVA) Early Treatment Diabetic Retinopathy Study letter score (approximate Snellen equivalent) in the study eye between 19 (20/400) and 78 (20/32), and spectral domain optical coherence tomography imaging central subfield thickness of 320 μm or greater. Data were analyzed from March 4, 2019, to April 26, 2019.Interventions: Participants were randomized (1:1:1) to receive repeated intravitreal injections of ranibizumab (0.5 mg/0.05 mL) (n = 155), aflibercept (2.0 mg/0.05 mL) (n = 154), or bevacizumab (1.25 mg/0.05 mL) (n = 154) for 100 weeks.Main Outcomes and Measures: Adjusted mean change in BCVA in the study eye at 100 weeks wherein noninferiority was concluded if the lower bounds of the 95% CI of both the intention-to-treat and the per protocol analyses were above –5 letters.Results: Of 463 participants, 265 (57.2%) were male, with a mean (SD) age of 69.1 (13.0) years. The mean (SD) gain in BCVA letter score was 12.5 (21.1) for ranibizumab, 15.1 (18.7) for aflibercept, and 9.8 (21.4) for bevacizumab at 100 weeks. Aflibercept was noninferior to ranibizumab (intention-to-treat–adjusted mean BCVA difference, 2.23 letters; 95% CI, –2.17 to 6.63 letters; P &lt; .001). Bevacizumab was not noninferior to ranibizumab (intention-to-treat–adjusted mean BCVA difference, –1.73 letters; 95% CI, –6.12 to 2.67 letters; P = .07). The per protocol analysis conclusions were similar. Fewer mean injections were given in the aflibercept group (10.0) than in the ranibizumab (11.8) group (mean difference at 100 weeks, –1.9; 95% CI, –2.9 to –0.8).Conclusions and Relevance: Mean changes in vision after treatment of macular edema due to CRVO were no worse using aflibercept compared with ranibizumab. Mean changes in vision using bevacizumab compared with ranibizumab were inconclusive regarding vision outcomes (ie, the change in visual acuity from baseline, on average, may be worse or may not be worse when using bevacizumab compared with ranibizumab)